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Letters A previous study suggested a regulatory function of sOSCAR by competing with membrane-bound OSCAR for its ligand. However, there is no evidence to suggest a mechanism by which elevated levels of sOSCAR could play a role in the pathogenesis of the observed association with RA severity and CVE risk. From our current understanding, sOSCAR levels could simply be associated with increased inflammation resulting in increased disease severity and cardiovascular risk. In conclusion, our results indicate that sOSCAR may represent a new relevant prognostic biomarker of joint destruction and CVE in RA. These preliminary results need to be confirmed in a larger number of patients and in other conditions. Ndiemé Ndongo-Thiam,1 Geoffroy de Sallmard,1 Jesper Kastrup,2 Pierre Miossec1 1
Immunogenomics and Inflammation Unit and the Department of Clinical Immunology and Rheumatology, Hospices Civils de Lyon, EA 4130 University of Lyon 1, Lyon, France 2 Novo Nordisk A/S, Måløv, Denmark Correspondence to Professor P Miossec, Department of Clinical Immunology and Rheumatology, Hôpital Edouard Herriot, 69437 Lyon, Cedex 03, France; [email protected] Acknowledgements We thank Guo Li and Chen Jianhe (Beijing Novo Nordisk Pharmaceuticals Science and Technology Co., Beijing, China) who provided tools for sOSCAR detection. Contributors NNT experiments and writing; GdS experiments; JK reagents; PM writing. Funding The study was supported in part by a grant from Novo Nordisk. NNT is supported by the IHU prometteur OPERA. Competing interests Professor Miossec is a senior member of and supported by the Institut Universitaire de France. Patient consent Obtained. Ethics approval Ethics committee of the hospitals of Lyon. Provenance and peer review Not commissioned; externally peer reviewed. To cite Ndongo-Thiam N, de Sallmard G, Kastrup J, et al. Ann Rheum Dis 2014;73:1276–1277. Received 8 November 2013 Accepted 2 January 2014 Published Online First 21 January 2014 Ann Rheum Dis 2014;73:1276–1277. doi:10.1136/annrheumdis-2013-204886
REFERENCES 1
2 3
4
5
Merck E, Gaillard C, Gorman DM, et al. OSCAR is an FcRgamma-associated receptor that is expressed by myeloid cells and is involved in antigen presentation and activation of human dendritic cells. Blood 2004;104:1386–95. Barrow AD, Raynal N, Andersen TL, et al. OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice. J Clin Invest 2011;121:3505–16. Herman S, Muller RB, Kronke G, et al. Induction of osteoclast-associated receptor, a key osteoclast costimulation molecule, in rheumatoid arthritis. Arthritis Rheum 2008;58:3041–50. Turesson C, McClelland RL, Christianson TJ, et al. Severe extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritis. Ann Rheum Dis 2007;66:70–5. Goettsch C, Rauner M, Sinningen K, et al. The osteoclast-associated receptor (OSCAR) is a novel receptor regulated by oxidized low-density lipoprotein in human endothelial cells. Endocrinology 2011;152:4915–26.
Antibodies against Porphyromonas gingivalis in seropositive arthralgia patients do not predict development of rheumatoid arthritis Clinical studies point towards an association between periodontitis and rheumatoid arthritis (RA).1 2 A pathogenic role is suggested for Porphyromonas gingivalis.3 P gingivalis may contribute to the pathogenesis of RA by breaking immune tolerance through Ann Rheum Dis June 2014 Vol 73 No 6
formation of (bacterial and human) citrullinated proteins, leading to anticitrullinated protein antibody production (ACPA).4 5 Since ACPA production precedes RA development6 and because P gingivalis IgG antibodies are long-term stable in untreated periodontitis patients,7 we investigated whether anti-P gingivalis antibody levels are prognostic for development of RA, by assessing these antibodies in a cohort of 289 adults at risk for RA. Patients with arthralgia and seropositivity for IgM-rheumatoid factor (IgM-RF) and/or ACPA were selected from a prospective follow-up study on arthritis development.8 They are further referred to as seropositive arthralgia patients (SAP); their median follow-up was 30 months (IQR 13–49). Baseline sera were used for measurement of ACPA, IgM-RF, C-reactive protein (CRP) and HLA-DRB1 SE carrier status.8 IgA, IgG and IgM antibody levels against P gingivalis were determined by in-house ELISA with a pooled lysate of clinical isolates of P gingivalis as antigen.9 Interference of IgM-RF on anti-P gingivalis antibody assays was excluded by spiking samples with sera with known high titres of RF. Reference groups for antibody levels against P gingivalis consisted of healthy subjects without periodontitis and without cultivable subgingival P gingivalis (HC, n=36, mean age 34 ±15 years, 53% female, 14% current smoker) and severe periodontitis patients without systemic disease (PD, n=117, mean age 51±9.3 years, 58% female, 43% current smoker, 42% P gingivalis-culture positive).10 Both groups were recruited among subjects planned for first consultation at the dental department of the University Medical Center Groningen and a referral practice for periodontology (Clinic for Periodontology Groningen).9 IgA and IgG anti-P gingivalis were higher in PD than in HC (both p
Letters A previous study suggested a regulatory function of sOSCAR by competing with membrane-bound OSCAR for its ligand. However, there is no evidence to suggest a mechanism by which elevated levels of sOSCAR could play a role in the pathogenesis of the observed association with RA severity and CVE risk. From our current understanding, sOSCAR levels could simply be associated with increased inflammation resulting in increased disease severity and cardiovascular risk. In conclusion, our results indicate that sOSCAR may represent a new relevant prognostic biomarker of joint destruction and CVE in RA. These preliminary results need to be confirmed in a larger number of patients and in other conditions. Ndiemé Ndongo-Thiam,1 Geoffroy de Sallmard,1 Jesper Kastrup,2 Pierre Miossec1 1
Immunogenomics and Inflammation Unit and the Department of Clinical Immunology and Rheumatology, Hospices Civils de Lyon, EA 4130 University of Lyon 1, Lyon, France 2 Novo Nordisk A/S, Måløv, Denmark Correspondence to Professor P Miossec, Department of Clinical Immunology and Rheumatology, Hôpital Edouard Herriot, 69437 Lyon, Cedex 03, France; [email protected] Acknowledgements We thank Guo Li and Chen Jianhe (Beijing Novo Nordisk Pharmaceuticals Science and Technology Co., Beijing, China) who provided tools for sOSCAR detection. Contributors NNT experiments and writing; GdS experiments; JK reagents; PM writing. Funding The study was supported in part by a grant from Novo Nordisk. NNT is supported by the IHU prometteur OPERA. Competing interests Professor Miossec is a senior member of and supported by the Institut Universitaire de France. Patient consent Obtained. Ethics approval Ethics committee of the hospitals of Lyon. Provenance and peer review Not commissioned; externally peer reviewed. To cite Ndongo-Thiam N, de Sallmard G, Kastrup J, et al. Ann Rheum Dis 2014;73:1276–1277. Received 8 November 2013 Accepted 2 January 2014 Published Online First 21 January 2014 Ann Rheum Dis 2014;73:1276–1277. doi:10.1136/annrheumdis-2013-204886
REFERENCES 1
2 3
4
5
Merck E, Gaillard C, Gorman DM, et al. OSCAR is an FcRgamma-associated receptor that is expressed by myeloid cells and is involved in antigen presentation and activation of human dendritic cells. Blood 2004;104:1386–95. Barrow AD, Raynal N, Andersen TL, et al. OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice. J Clin Invest 2011;121:3505–16. Herman S, Muller RB, Kronke G, et al. Induction of osteoclast-associated receptor, a key osteoclast costimulation molecule, in rheumatoid arthritis. Arthritis Rheum 2008;58:3041–50. Turesson C, McClelland RL, Christianson TJ, et al. Severe extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritis. Ann Rheum Dis 2007;66:70–5. Goettsch C, Rauner M, Sinningen K, et al. The osteoclast-associated receptor (OSCAR) is a novel receptor regulated by oxidized low-density lipoprotein in human endothelial cells. Endocrinology 2011;152:4915–26.
Antibodies against Porphyromonas gingivalis in seropositive arthralgia patients do not predict development of rheumatoid arthritis Clinical studies point towards an association between periodontitis and rheumatoid arthritis (RA).1 2 A pathogenic role is suggested for Porphyromonas gingivalis.3 P gingivalis may contribute to the pathogenesis of RA by breaking immune tolerance through Ann Rheum Dis June 2014 Vol 73 No 6
formation of (bacterial and human) citrullinated proteins, leading to anticitrullinated protein antibody production (ACPA).4 5 Since ACPA production precedes RA development6 and because P gingivalis IgG antibodies are long-term stable in untreated periodontitis patients,7 we investigated whether anti-P gingivalis antibody levels are prognostic for development of RA, by assessing these antibodies in a cohort of 289 adults at risk for RA. Patients with arthralgia and seropositivity for IgM-rheumatoid factor (IgM-RF) and/or ACPA were selected from a prospective follow-up study on arthritis development.8 They are further referred to as seropositive arthralgia patients (SAP); their median follow-up was 30 months (IQR 13–49). Baseline sera were used for measurement of ACPA, IgM-RF, C-reactive protein (CRP) and HLA-DRB1 SE carrier status.8 IgA, IgG and IgM antibody levels against P gingivalis were determined by in-house ELISA with a pooled lysate of clinical isolates of P gingivalis as antigen.9 Interference of IgM-RF on anti-P gingivalis antibody assays was excluded by spiking samples with sera with known high titres of RF. Reference groups for antibody levels against P gingivalis consisted of healthy subjects without periodontitis and without cultivable subgingival P gingivalis (HC, n=36, mean age 34 ±15 years, 53% female, 14% current smoker) and severe periodontitis patients without systemic disease (PD, n=117, mean age 51±9.3 years, 58% female, 43% current smoker, 42% P gingivalis-culture positive).10 Both groups were recruited among subjects planned for first consultation at the dental department of the University Medical Center Groningen and a referral practice for periodontology (Clinic for Periodontology Groningen).9 IgA and IgG anti-P gingivalis were higher in PD than in HC (both p
